Nosocomial infections are the fourth leading cause of death in the U.S. with >2 million cases annually (or ~10% of American hospital patients). About 60% of these infections are associated with an implanted medical device causing >$4.5 billion medical costs in 2010 and ~90,000 deaths annually. It is estimated that over 5 million artificial o prosthetic parts are implanted per annum in the U.S. alone. Our goal, with renewal NIH support, is to engineer biomaterials that will solicit a short---innate and long---term adaptive immune response to specific bacterial colonization. For short---term immediate defense, model biomaterials will release bi-specific fusion protein complexes designed to enhance the coupling (and ultimately phagocytosis) of invading Gram--- positive and Gram---negative species to monocyte/macrophage (M). For long---term protection, the biomaterial will transfect antigen---presenting cells (specifically dendritic cells --- DCs) with novel self---amplifying mRNA vaccines to an engineered adaptive immune response. Target bacteria will be expanded from Staphylococcus epidermidis to Pseudomonas aeruginosa and Enterococcus faecalis.